Genetic diagnostic criteria | Either TSC1 or TSC2 pathogenic# mutation in DNA from normal tissue |
Clinical diagnostic criteria | |
Major features | Hypomelanotic macules (≥3, ≥5 mm diameter) Angiofibromas (≥3) or fibrous cephalic plaque Ungual fibromas (≥2) Shagreen patch Multiple retinal hamartomas Cortical dysplasias (includes tubers and cerebral white matter radial migration lines) Subependymal nodules Subependymal giant cell astrocytoma Cardiac rhabdomyoma LAM¶,+ Angiomyolipomas (≥2)+ |
Minor features | “Confetti” skin lesions Dental enamel pits (>3) Intraoral fibromas (≥2) Retinal achromic patch Multiple renal cysts Nonrenal hamartomas |
Diagnosis | |
Definite | Genetic criteria OR Two major features OR One major feature with ≥2 minor features |
Possible | Either one major feature OR ≥2 minor features |
LAM: lymphangioleiomyomatosis. #: defined as a mutation that clearly inactivates the function of the TSC1 or TSC2 proteins (e.g. out-of-frame insertion/deletion or nonsense mutation), prevents protein synthesis (e.g. large genomic deletion) or is a missense mutation whose effect on protein function has been established by functional assessment. Other TSC1 or TSC2 variants whose effect on function is less certain do not meet these criteria, and are not sufficient to make a definite diagnosis of TSC; ¶: see table 3; +: a combination of LAM and angiomyolipomas without other features does not meet criteria for a definite diagnosis. Information from [1].